According to the report of World Health Organization (WHO), the number of people died from atherosclerosis (AS) accounts for 52% of the number of people died from all diseases, which is far more than the number of people died from tumours that is the second cause of death (24%) and atherosclerosis has become the first killer threatening human's health. AS mainly involves large and medium scale muscle tension type arteries, wherein thickening of the arterial wall and luminal stenosis are main basis of clinical imaging diagnosis. However, recent studies indicate that the occurrence of clinical events caused by AS, such as acute coronary syndrome, always has no significant relevance with the arterial stenosis caused by AS. The appearance and development of AS is a chronic and progressive process, typical AS conditions can be seen in young adults, but it is not easily to be detected, and serious clinical manifestations always appears a dozen years or several decades latter. Early diagnosis and intervention are crucially important to the disease development and prognosis of AS patients.
Current AS imaging diagnostic technologies are classified into two categories:
1. invasive diagnostic technologies: now they are considered as “gold standard” for diagnosing AS, and comprise intravascular ultrasound, digital angiography, and angioscopy, all of them are invasive diagnostic technologies, wherein a catheter has to be inserted for forming images, their operations are complex, and they have a certain dangerousness and complications;
2. noninvasive AS diagnostic technologies comprise 1) multi-slice helical CT, which can obtain 256 slices simultaneously in less than 25 ms, and can provide an intact coronary angiography within 15 s. Its limitations are that in order to ensure image quality, the heart rate has to be decreased, and the spatial resolution is not high, limited by the time resolution, partial volume effect affects its density measurement, and at noncalcified plaques, especially at places with non-significant stenosis, plaques and blood vessel walls cannot be distinguished; 2) CT angiography, when being, used for AS diagnosis, the display of lesion areas is interfered by skeletal images, removing skeletal images by post processing consumes a long time and the effect is not good.
Magnetic resonance angiography (MRA) is a noninvasive diagnostic technology used for diagnosis of blood vessel diseases in magnetic resonance imaging (MRI); the technology can display the stenosis degree by blood flow imaging, and avoid the disadvantages such as using a nephrotoxic contrast agent and ionizing radiation and the like in CT blood vessel image technology. MRI black blood technique (an imaging technique for observing blood vessel walls by means of the blood flow darkening) can accurately describe initial data, such as the existences, sizes and morphologies etc. of plaques at a high resolution and repeatability, so as to indicate that using MRI for evaluating blood vessel walls is feasible. MRI is suitable for all blood vessel areas, but now mainly used for peripheral angiography, there still are some challenges in the examination of coronary artery diseases, this is mainly because that the diameter of coronary artery is small, the direction thereof is bend, MRI is easily affected by respiration and heart rate, the scanning time is too long and the spatial resolution is low. During MRI imaging for coronary arteriosclerosis, the current bottleneck problem is how to improve the resolution of magnetic resonance images. Ultra-small superparamagnetic iron oxide (USPIO) is constituted by a single crystal core consisting of Fe3O4 or Fe2O3 and an outer layer coating. After entering into an applied magnetic field, USPIO particles are distributed unevenly, which makes a non-uniform local magnetic field, generates a magnetizing effect, thus accelerates T2 relaxation of proton dephasing, decreases signals of the tissue where they locates, but their influence to T1 relaxation is relatively small, thus making them have properties of a relatively good negative contrast agent. The half life of USPIO is long, R1/R2 of USPIO is appropriate, and USPIO is low-osmotic in normal blood vessels, so USPIO can perform a first pass imaging and a high resolution scanning in the balanced phase. USPIO can be recognized and swallowed by macrophagocytes in AS plaques, so they can mark AS plaques. Schmitz et al. found that in a part of tumour patients of lymph node mapping, USPIO is swallowed by macrophagocytes in the body, and it can be detected that the focal signal ratio in the inflammatory areas of AS plaques decreases. In animal models, it is demonstrated that the positive rate of iron microparticle histological examination in plaques significantly rises as the dosage increases, and USPIO mainly deposits on unstable plaques, and can be effectively imaged in MRI. Researchers have used USPIO as the contrast agent in MRA for observing renal artery and coronary artery, as a result, they found that the imaging effect of the contrast agent for distal blood vessels and their branches is significant.
However, since there is no targeting guidance, after injected into the body, USPIO mainly are uptaken by Reticuloendothelial system (RES); USPIO has some targeting effect for AS blood vessels but the requirement of clinical diagnosis is difficult to achieve. Therefore, how to realize the targeting enrichment of USPIO in AS blood vessels, it is an important research direction for improving the accuracy rate in MRI diagnosis of AS.